tbuckley/cabot-search huggingface dataset:
Cancer treatment and survivorship statistics, 2022
Authors: Kimberly D. Miller, Leticia Nogueira, Theresa Devasia, Angela B. Mariotto, K. Robin Yabroff, Ahmedin Jemal, Joan Kramer, Rebecca L. Siegel
Journal: CA A Cancer Journal for Clinicians (2022)

The number of cancer survivors continues to increase in the United States due to the growth and aging of the population as well as advances in early detection and treatment. To assist the public health community in better serving these individuals, the American Cancer Society and the National Cancer Institute collaborate triennially to estimate cancer prevalence in the United States using incidence and survival data from the Surveillance, Epidemiology, and End Results cancer registries, vital statistics from the Centers for Disease Control and Prevention's National Center for Health Statistics, and population projections from the US Census Bureau. Current treatment patterns based on information in the National Cancer Database are presented for the most prevalent cancer types by race, and cancer-related and treatment-related side-effects are also briefly described. More than 18 million Americans (8.3 million males and 9.7 million females) with a history of cancer were alive on January 1, 2022. The 3 most prevalent cancers are prostate (3,523,230), melanoma of the skin (760,640), and colon and rectum (726,450) among males and breast (4,055,770), uterine corpus (891,560), and thyroid (823,800) among females. More than one-half (53%) of survivors were diagnosed within the past 10 years, and two-thirds (67%) were aged 65 years or older. One of the largest racial disparities in treatment is for rectal cancer, for which 41% of Black patients with stage I disease receive proctectomy or proctocolectomy compared to 66% of White patients. Surgical receipt is also substantially lower among Black patients with non-small cell lung cancer, 49% for stages I-II and 16% for stage III versus 55% and 22% for White patients, respectively. These treatment disparities are exacerbated by the fact that Black patients continue to be less likely to be diagnosed with stage I disease than White patients for most cancers, with some of the largest disparities for female breast (53% vs 68%) and endometrial (59% vs 73%). Although there are a growing number of tools that can assist patients, caregivers, and clinicians in navigating the various phases of cancer survivorship, further evidence-based strategies and equitable access to available resources are needed to mitigate disparities for communities of color and optimize care for people with a history of cancer. CA Cancer J Clin. 2022;72:409-436.
P1435: PRECLINICAL EVALUATION OF ZILOVERTAMAB-BASED ANTI-ROR1 CHIMERIC ANTIGEN RECEPTORS IN NK AND T CELLS
Authors: S. Meinke, N. Kadri, S. Bi, B. Bostancioglu, C. Markey, J. B. Breitmeyer, A. Hussain, R. Krishnan, G. F. Kaufmann, E. Alici
Journal: HemaSphere (2022)

Background: The receptor tyrosine kinase-like orphan receptor ROR1 is a promising target for immunotherapies of many cancers, including mantle cell lymphoma, diffuse large B-cell lymphoma, B-cell acute lymphocytic leukemia and chronic lymphocytic leukemia. Normally only expressed during embryonic development and only minimally, if at all, in adult normal tissues, ROR1 is overexpressed on malignant cells. Zilovertamab is a monoclonal antibody binding ROR1 that is currently in Phase 1/2 clinical trials. The antibody blocks survival signals mediated by Wnt5a via the ROR1 receptor. A different approach is the use of the antigen binding domain of the antibody in chimeric antigen receptors (CARs) expressed in NK or T cells to induce cellular cytotoxicity against ROR1-expressing cancer cells. Aims: This study aimed to evaluate different CAR designs in NK cells and T cells for cytotoxicity and cytokine production in vitro and control of cancer growth in a murine in vivo model. Methods: Two CARs using different linkers between the single chain antibody fragment (scFv) and the transmembrane domain were designed and cloned into lentiviral vectors. The two constructs were expressed in the cell line NK92 and the cells’ response against ROR1-positive and negative cancer cell lines was measured by degranulation and interferon-γ production. The construct that showed a stronger activation was tested in an in vivo model. Immune deficient NSG mice were injected with ROR1-positive JEKO-1 cells transgenic for luciferase. The cancer cell burden was monitored by intravital imaging. When cancer cell growth was established, the mice received either 1, 3, or 9 x 106 human T cells expressing the CAR or untransduced T cells. Results: NK92 cells expressing either of the two CARs showed enhanced degranulation and IFN-γ production in response to the ROR1-expressing cancer cell lines RPMI 8226 and JEKO-1. NK cells expressing the CAR containing the shorter linker between the scFv and the transmembrane domain exhibited higher activation levels. Primary human T cells expressing this CAR construct demonstrated degranulation and cytokine production during co-incubation with the ROR1-expressing JEKO-1 cell line but not the ROR1-negative Jurkat cell line. Injection of anti-ROR1 human CAR-T cells into NSG mice with established cancer growth greatly reduced the cell burden of JEKO-1 while untransduced T cells were unable to control cancer cell growth. Summary/Conclusion: The zilovertamab-based CAR tested in this study enhances the NK cell response towards ROR1-expressing cancer cells and enables T cells to clear fast-growing cancer cells in an in vivo model. These findings support the development of anti-ROR1 cell therapies for the potential treatment of ROR1-positive hematological malignancies.
P1193: A POPULATION PHARMACOKINETIC MODEL OF HIGH-DOSE METHOTREXATE IN ADULTS WITH CANCER IDENTIFIES BASELINE ALBUMIN, BODY WEIGHT, AND TIME-DEPENDENT CREATININE AS PREDICTORS OF ACUTE KIDNEY INJURY
Authors: S. Howard, M. Ibarra, R. Combs, P. Schaiquevich
Journal: HemaSphere (2022)

Background: High-dose methotrexate (HDMTX) is an essential part of the treatment of several adult and pediatric malignancies. Despite meticulous supportive care during HDMTX administration, severe toxicities can occur, including acute kidney injury (AKI) which can delay methotrexate elimination, prolong hospital stay, delay subsequent anticancer therapy, and contribute to morbidity. Population pharmacokinetics provide a powerful tool to predict the time to clear HDMTX and adjust doses for subsequent courses. Aims: We developed and validated pharmacokinetic models for adults with diverse malignancies and related their systemic exposure to methotrexate to the incidence of serious toxicity. Methods: Anonymized, de-identified data were provided from 101 US oncology practices that participate in the Guardian Research Network, a non-profit clinical research consortium with access to entire electronic medical records, including clinical information, drug treatments with dose and route of administration, laboratory values, procedures, notes, and reports. Modeled variables included clinical, laboratory, demographic, and pharmacological data. Population pharmacokinetic analysis was performed on all adults who received HDMTX using nonlinear mixed effects modeling with MonolixSuite. Results: A total of 708 HDMTX courses from 258 adults were analyzed, of which 90 (13%) were associated with acute kidney injury within 48 hours of the start of HDMTX and 31% with delayed methotrexate elimination (>2 standard deviations above the mean). A three-compartment model adequately fit the data, and a combination of time-dependent serum creatinine, baseline albumin, and allometrically scaled body weight best predicted methotrexate clearance. The 3-compartment model was validated using two reference datasets from adults receiving HDMTX as short or long infusions. Dose-normalized methotrexate concentration at 24 and 48 hours correlated with AKI. Patients with AKI who did not receive glucarpidcase experienced significantly longer hospital length of stay (p<0.01) and time to methotrexate elimination (p<0.01). Summary/Conclusion: We developed a population pharmacometric model of HDMTX elimination that considers weight, albumin, and time-dependent creatinine to predict AKI and guide supportive care in patients with delayed HDMTX elimination.
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Journal: JAMA Network Open (2022)

Taya A. Collyer, PhD; Anne M. Murray, MD; Robyn L. Woods, PhD; Elsdon Storey, MBBS, DPhil; Trevor T.-J. Chong, MBBS, PhD; Joanne Ryan, PhD; Suzanne G. Orchard, PhD; Amy Brodtmann, MBBS, PhD; Velandai K. Srikanth, MBBS, PhD; Raj C. Shah, MD; Michele L. Callisaya, PhD
P1136: INTERIM IMAGING DOES NOT PREDICT CLINICAL EVOLUTION IN FOLLICULAR LYMPHOMA IN A REAL-LIFE CLINICAL SETTING
Authors: V. Ramos De Ascanio, L. Sánchez Paz, M. S. Infante, J. Churruca Sarasqueta, M. Á. Foncillas García, E. Landete Hernández, K. D. C. Marín Mori, C. Muñoz Novas, J. Á. Hernández Rivas, I. González Gascón y Marín
Journal: HemaSphere (2022)

Background: Interim scan evaluation is a common practice during the treatment of some types of lymphomas with (immuno)-chemotherapy (ICT). In follicular lymphoma (FL) its role remains controversial and few studies have looked at this topic specifically. However, it is performed in clinical practice, clinical trials and recommended by some international guidelines (ESMO). Aims: In this study, we analyzed the clinical and prognostic value of interim imaging (iPET/iCT) during the first line-treatment of patients diagnosed with FL. Methods: In order to execute this, we carried out a retrospective analysis of all FL patients that received a first line treatment (ICT) at our institution and underwent an iPET/iCT between 2008 and 2021. Patients with Grade 3b or histologic transformation were excluded from the analysis. All data was extracted from electronical medical records. The Lugano response criteria were used to assess disease response. Statistical analysis was performed using SPSS version 25.0 and survival was estimated by Kaplan-Meier curves and log rank tests. Results: Baseline characteristics of patients included in this study are described in Table 1. Median follow-up was 71 months (6-153). All patients underwent iPET/iCT (iCT=52 (81.3%); iPET=12 (18.8%)). Most iPET/iCT showed a partial response (PR) (n=48, 75%), and a minority a complete response (CR) (n=14, 21.9%). Two patients (3.1%) did not respond to induction. The 14 patients with CR maintained the response at the end of induction; 34 of 48 PR patients (70.8%), achieved a CR on final imaging; whereas 14 patients (29.2%) maintained a PR. Out of the 64 patients, 17 (26.6%) had disease progression during the observation period. In 6 patients (9.4%) interim imaging conditioned a treatment modification (premature discontinuation of therapy, increase/decrease in the number of ICT cycles or ICT dose attenuation). No significant differences were found in progression-free survival (PFS) (p=0.3) between the 14 patients with CR and the 48 patients who showed PR or less in the interim imaging. Nevertheless, patients in PR who converted to CR at the end of therapy had a significantly higher PFS than patients who did not achieve CR at the end of induction (p<0.01). Consequently, patients who reached a CR at the end of therapy achieved a significantly higher PFS compared to those who did not (p<0.01). Image:Summary/Conclusion: Obtaining an early CR on interim imaging did not predict PFS in FL patients treated with IQT. In addition, clinical decisions based on iPET/iCT were only made in a minority of the patients, with the detection of early refractoriness being residual. Conversely, end of treatment imaging assessment was a useful tool capable of predicting PFS.
P607: A NOVEL LYMPH NODE-MIMICKING 3D CULTURE SYSTEM DISPLAYS LONG-TERM T CELL-DEPENDENT CLL PROLIFERATION AND SURVIVAL
Authors: M. Haselager, E. Perelaer, A. Kater, E. Eldering
Journal: HemaSphere (2022)

Background: Primary chronic lymphocytic leukemia (CLL) cells, despite originating from a proliferative disease, rapidly undergo apoptosis in vitro in the absence of microenvironmental survival signals1. No current system permits long-term expansion of CLL cells in vitro due to difficulties of mimicking a physiological microenvironment. The lymph node (LN) is the critical site of in vivo CLL proliferation and is also thought to play a key role in the development of resistance to targeted agents2,3. Developing an in vitro culture system for CLL with pathophysiological relevance will greatly benefit studies of CLL proliferation, microenvironment, clonal outgrowth and relevant drug screening. Aims: To design an in vitro CLL culture system that incorporates key aspects of the CLL LN; contribution of non-CLL cells and cytokines, and induction of drug resistance and prolonged proliferation of CLL cells. Methods: Primary CLL cells were cultured in ultra-low attachment (ULA) plates in parallel to standard 2D cultures. PBMCs were cultured with or without T cells (in a specific CLL:T cell ratio to mimic the LN composition), or PBMCs were co-cultured with primary lymph node fibroblasts. CLL cells were either stimulated directly with a B cell cocktail (BCC) consisting of IL-2, IL-15, IL-21 and CpG and/or indirectly via a T cell stimulation of anti-CD3/CD28. Results: Compared to 2D cultures, 3D cultures showed several important CLL LN features. First, significantly increased CLL proliferation independent of IGHV mutation status, which was abrogated in the absence of T cells, or by JAK inhibitors. Notably, treatment with BTK inhibitors significantly inhibited CLL proliferation and resulted in disintegration of the 3D spheroid architecture. Second, co-culture with LN-derived stromal cells further increased CLL proliferation, reaching a maximum of 8 generations. Third, 3D cultures could be expanded approximately 3-4-fold over a course of 6 weeks using the 3D model. Fourth, when PBMCs were stimulated with BCC, spheroids developed proliferation center-like structures after 4 weeks of culture where T cells localized together with enrichment of Ki-67+ CLL cells. Finally, either B or T cell stimulation resulted in an induction of venetoclax resistance, showing that T cells are able to confer drug resistance to CLL cells in this model. Summary/Conclusion: We present a 3D culture system that underlines the role of T cells in sustained CLL proliferation, permitting investigation of CLL cells in the context of a protective niche consisting of multiple cell types, thereby opening up new avenues for clinically useful applications.
Chlorella sp.-ameliorated undesirable microenvironment promotes diabetic wound healing
Authors: Hangyi Wu, Pei Yang, Aiqin Li, Xin Jin, Zhenhai Zhang, HuiXia Lv
Journal: Acta Pharmaceutica Sinica B (2022)

Chronic diabetic wound remains a critical challenge suffering from the complicated negative microenvironments, such as high-glucose, excessive reactive oxygen species (ROS), hypoxia and malnutrition. Unfortunately, few strategies have been developed to ameliorate the multiple microenvironments simultaneously. In this study, Chlorella sp. (Chlorella) hydrogels were prepared against diabetic wounds. In vitro experiments demonstrated that living Chlorella could produce dissolved oxygen by photosynthesis, actively consume glucose and deplete ROS with the inherent antioxidants, during the daytime. At night, Chlorella was inactivated in situ by chlorine dioxide with human-body harmless concentration to utilize its abundant contents. It was verified in vitro that the inactivated-Chlorella could supply nutrition, relieve inflammation and terminate the oxygen-consumption of Chlorella-respiration. The advantages of living Chlorella and its contents were integrated ingeniously. The abovementioned functions were proven to accelerate cell proliferation, migration and angiogenesis in vitro. Then, streptozotocin-induced diabetic mice were employed for further validation. The in vivo outcomes confirmed that Chlorella could ameliorate the undesirable microenvironments, including hypoxia, high-glucose, excessive-ROS and chronic inflammation, thereby synergistically promoting tissue regeneration. Given the results above, Chlorella is considered as a tailor-made therapeutic strategy for diabetic wound healing.
P1349: EFFECT OF TRANSPLANTED CD184-POSITIVE CELLS (WITH EXPRESSION CXCR4) FOR A LONG SURVIVAL AFTER AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION IN MULTIPLE MYELOMA – ONE CENTER PROSPECTIVE STUDY.
Authors: A. Kopinska, A. Wieczorkiewicz, A. Koclega, K. Jagoda, J. Dziaczkowska-Suszek, G. Helbig
Journal: HemaSphere (2022)

Background: Autologous hematopoietic stem cell transplantation (AHSCT) remains the treatment of choice in multiple myeloma (MM) patients (pts). The role of chemokine CXCR4 knows also as CXCR4 in hematopoietic stem cell homing engraftment, and in hematopoietic recovery after AHSCT is still not fully understood as well. Aims: In this prospective study we would like to investigate the influence CD184+ cells for overall survival (OS) and progression free survival (PFS) after AHSCT in MM pts. Methods: Forty eight pts with MM with median age 56 (range 21-76) were undergoing AHSCT in our center in years 2011-2013. Conditioning regimen was Melphalan. Number of all CD184+ cells were measured in harvested material. Results: All pts successfully engrafted. The median follow-up was over 8 years. Currently 21 pts (44%) are alive, including 8 pts (17%) in disease’s remission, and 13 are treated for MM progression. Twenty-seven pts died including 19 pts due to disease progression. The median OS was 7.8 years. In the study group a statistically significant correlation was found between OS, PFS and the number of CD184+ cells. In the context of OS and PFS, number of CD184+ cells was found to have a negative impact (correlation coefficient R = -0.32, p=0.0261, and correlation coefficient R = -0.41, p=0.0039 for OS and PFS retrospectively). As OS and PFS increased, the number of CD184+ cells decreased. Summary/Conclusion: The number of CD184+ cells could have a negative effect on both OS and PFS in multiple myeloma patients.
P1382: RUXOLITINIB USE IN A REAL WORLD ACUTE AND CHRONIC GRAFT VERSUS HOST DISEASE COHORT IN THE NETHERLANDS: A RETROSPECTIVE STUDY
Authors: L. Van Der Wagen, S. van Dorp, M. Bellido Cassado, F. Verheij, K. Nijssen, W. van der Velden, A. Biswana, N. Blijlevens, J. Kuball
Journal: HemaSphere (2022)

Background: Preclinical data showed that Janus Kinase (JAK) signaling plays an important role in the pathogenesis of Graft versus Host Disease (GVHD) and several clinical studies showed remarkable clinical efficacy in both acute and/or chronic steroid-refractory (SR)-GVHD patients. However, these clinical results have not yet been repeated in real world cohorts with long term follow-up. Furthermore, infectious complications have not been highlighted in published clinical trials whilst these remain a significant problem in daily practice. Aims: To assess the response of acute and/or chronic SR-GVHD patients to ruxolitinib treatment and to assess side-effects of ruxolitinib treatment occurring in adult acute and/or chronic SR-GVHD patients. Methods: We performed a retrospective analysis of 121 consecutive patients treated with ruxolitinib for either acute or chronic GVHD. Patients were included from 3 academic centers in the Netherlands from 2014 to 2019. Patients provided written informed consent, with the exception of deceased patients in accordance with the local ethics committee. Patient data were extracted by personnel from an independent CRO to minimize reviewer bias. Patient data were anonymized. Results: 121 patients were included in the study of whom 54 were diagnosed with acute and 67 patients with chronic GVHD. Selected baseline characteristics are depicted in Table 1. The overall response rate at day 28 of acute GVHD was 70% (38/54) with a complete response in 50% of patients (27/54). At timepoint 6 months after initiation of ruxolitinib for chronic GVHD, the majority of patients showed stable disease. The overall response rate at 6 months in chronic GVHD was 28% (19/67) with a complete response in 13% of patients (9/67). Ruxolitinib use was mainly complicated by infections and hematological toxicity. Of the reported (S)AE’s possibly related to ruxolitinib, 38% were infectious and 13% were hematological. Severity of infections ranged from grade 1 to grade 5, median grade 2. Most infections were viral (43%), followed by bacterial (19%) and fungal or mould infections (14%). During follow up mortality was 14,9% (18 patients) of which 6 cases were due to uncontrolled GVHD, 5 cases due to infections and 3 patients died of relapse of their primary malignancy, 4 patients died of other causes. Image:Summary/Conclusion: In a real world cohort of GVHD patients treated with ruxolitinib we observed in patients with acute GVHD a complete response rate at day 28 of 50%. Overall response rate at 6 months in cGVHD patients was 28%. Infectious adverse events were common in both acute and chronic GVHD patients and were mainly caused by viral pathogens.
P1151: METABOLIC TUMOR VOLUME IMPROVES OUTCOME PREDICTION IN UNTREATED MANTLE CELL LYMPHOMA
Authors: V. K. Vergote, G. Verhoef, A. Janssens, F. S. Woei-a-jin, A. Laenen, T. Tousseyn, D. Dierickx, C. M. Deroose
Journal: HemaSphere (2022)

Background: Mantle cell lymphoma (MCL) is a rare, incurable subtype of B-cell non-Hodgkin’s lymphoma, with heterogenous clinical behavior ranging from indolent to very aggressive disease course with rapid relapses and short survival. Aims: The aim of this retrospective study is to analyze the prognostic value of baseline [18F]FDG-PET/CT metabolic parameters in untreated MCL. Methods: We retrospectively analyzed baseline [18F]FDG-PET/CT of patients in our institution (University Hospitals Leuven, Belgium) with histopathological confirmed newly diagnosed MCL between January 1st 2004 and 31st December 2020. Maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), peak standardized uptake value (SUVpeak), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were analyzed. Lesion dissemination (Dmax) and lesion dissemination standardized to body surface area (SDmax) were calculated. Univariate and multivariate analysis were performed using Cox proportional hazard models. Kaplan Meier survival curves were constructed. Results: We included 83 patients with a median age of 66 years. The median MTV was 141.5 ml and the median Dmax was 0.6 m. A median follow-up of 47 months was achieved. In total 42 patients died. Higher MTV was an adverse factor for overall survival (OS) (p=0.0137; hazard ratio (HR): 1.48; 95% confidence interval (CI): 1.08-2.03), progression-free survival (PFS) (p=0.0106; HR: 1.41; 95% CI: 1.08-1.84) and disease-specific survival (DSS) (p=0.0366; HR: 1.56; 95% CI: 1.03-2.36). Furthermore, higher age at diagnosis, MCL International Prognostic Index-score (MIPI) and Eastern Cooperative Oncology Group Performance status (ECOG PS) were adverse factors for OS, PFS and DSS. We found no significant correlation between Dmax, SDmax and any of the outcomes considered. In multivariate analysis accounting for clinical characteristics, MTV was significantly associated with DSS (p=0.0072; HR: 1.53; 95% CI: 1.12-2.08), but not with OS and PFS. OS in the patients with MTV above the median (high, ≥141 ml) was significantly worse compared to the group with low MTV (<141 ml) (median OS 6.1 years versus 7.6 years; p=0.0077). Furthermore, there was a significant difference in PFS (median 2.9 versus 5.0 years; p=0.0055) and DSS (median 7.3 years versus not reached; p=0.0219) between the groups with high and low MTV. MTVspleen was an adverse factor for OS (p=0.0103; HR: 1.36; 95% CI: 1.08-1.72) and PFS (p=0.0019; HR: 1.40; 95% CI: 1.13-1.72) in multivariate analysis. Ann Arbor stage was not withheld as a significant factor for outcome prediction in univariate nor multivariate analysis. Summary/Conclusion: MTV is an important prognostic tool and can further improve patient risk stratification at staging of untreated MCL. We found no correlation between lesion dissemination (Dmax, SDmax) on [18F]FDG-PET/CT and outcome.